Two neurophysiological abnormalities, a deficit in the gating of the auditory evoked potential wave P50 in the conditioning- testing paradigm and a deficit in smooth pursuit eye movements (SPEM), are frequently found in both schizophrenics and in their relatives. The principal aim of this Project, in conjunction with Project 2, is to determine if these two neurophysiological abnormalities represent phenotypic expressions of the gene or genes which convey risk for schizophrenia. Multigenerational families including schizophrenic probands, recruited in Utah, will be evaluated for both abnormalities. The neurophysiological phenotypes will then be genotyped using complementary DNA techniques, to determine if either or both measures can be linked to specific genetic loci. Deficits in P50 gating and SPEM are both thought to be examples of the problems in sensory gating which seem to underlie the psychopathology of schizophrenia. However, a comprehensive understanding of the neurobiology of sensory gating has not yet been achieved. The goal of Project 3 is to describe the neurobiology of P50 gating in laboratory animal models. As better descriptions of the neurobiology are obtained, Project 1 will determine if better measures of sensory gating can be added to the P50 gating and SPEM measurements in current use. Our overall goal in Project 1 is to demonstrate as precisely as possible the phenotypic expression of the gene of genes which convey genetic risk for schizophrenia.